1. Field of the Invention
This invention relates to a novel process for producing cyclodextrins and more particularly, to a process for producing cyclodextrins without using any organic solvents, which comprises passing a solution containing cyclodextrins and reducing sugars as primary ingredients through a column packed with alkali or alkali earth metal salts of strongly acidic cation exchange resin to separate and collect cyclodextrins from the sugar solution.
2. Description of the Prior Art
Cyclodextrins are non-reducing dextrins which have a ring structure wherein glucose units are joined to one another by .alpha.-1,4-glucosidic linkages. Generally, .alpha.-cyclodextrin, .beta.-cyclodextrin and .gamma.-cyclodextrin, which consist of 6, 7 and 8 glucose units, respectively, are well known. The cyclodextrin molecule includes various kinds of organic compounds into the cavity of the ring structure which is in a hydrophobic atmosphere to form an inclusion compound. Alpha-, beta- and gamma-cyclodextrins have many different physical properties from one another: the molecular weights (.alpha.=973, .beta.=1135 and .gamma.=1297), the cavity diameters of ring structure (.alpha.=5-6 A, .beta.=7-8 A and .gamma.=9-10 A) and water solubility (at 25.degree. C., g/100 ml.H.sub.2 O: .alpha.=14.5, .beta.=1.85 and .gamma.=23.2).
Accordingly, cyclodextrins find wise use in medicines, agricultural chemicals, cosmetics and foods and new applications thereof are expected to be found. Only a mixture of .alpha.-, .beta.- and .gamma.-cyclodextrins and starch hydrolyzate containing acyclic dextrins, and, .beta.-cyclodextrin precipitated and separated from such mixture, are products which can be produced, at present, at relatively low cost. Alpha-cyclodextrin and .gamma.-cyclodextrin cannot be produced at low cost. The industrial production of .alpha.- and .gamma.-cyclodextrins is deemed difficult, although they have special properties and their specific applications are expected as described above. This is due to the difference of water solubility of .alpha.-, .beta.- and .gamma.-cyclodextrins. Namely, the water-solubility of .beta.-cyclodextrin is very low compared with .alpha.- and .gamma.-cyclodextrins and therefore, it is easily precipitated and separated from the starch hydrolyzate solution containing cyclodextrins. On the contrary, .alpha.- and .gamma.-cyclodextrins have relatively high water solubilities and so, it is difficult without using any organic solvents to separate these cyclodextrins as crystal from the starch hydrolyzate solution containing cyclodextrins.
There are many proposed processes for producing cyclodextrins hereinbefore. One typical process is such that liquefied starch products are reacted with cyclodextrin glycosyltransferase, hereinafter refer to "CGTase," to obtain starch hydrolyzate solution containing cyclodextrins followed by adding an organic solvent such as trichloroethylene, tetrachloroethane or bromobenzene to precipitate cyclodextrins as a complex and to separate cyclodextrins from the starch hydrolyzate.
An improved process of the typical one mentioned above has been proposed, which comprises reacting the starch hydrolyzate containing cyclodextrins with glucoamylase in order to hydrolyse acyclic dextrins to convert them into glucose and then adding an organic solvent to the resulting sugar solution containing cyclodextrins and glucose to precipitate only cyclodextrins (see DENPUN-KAGAKU (Starch Science) 22, pp. 6-10 (1975): Japanese Pat. No. 1,034,493).
However, organic solvents are used to precipitate cyclodextrins in all the aforementioned processes and contaminate the cyclodextrins thus obtained so that they cannot be utilized in the production of medicines or foods due to the toxicity of the solvents and the production cost should have been high.
Some processes for producing cyclodextrins without using any organic solvents, that is, non-solvent processes have recently been discussed and proposed. There are proposed two non-solvent processes, that is, the one comprising reacting liquefied starch with a new CGTase having an optimum pH on the alkaline side instead of known CGTases, concentrating the reaction mixture and adding a small amount of cyclodextrin as a seed crystal to precipitate cyclodextrins (see Japanese Pat. No. 914,137) and the other comprising contacting a solution containing cyclodextrins and reducing sugars with OH type of anion exchange resin to adsorb only reducing sugars on the resin to thereby separate cyclodextrins from the reducing sugars (see Japanese Pat. No. 136,889/1976).
These non-solvent processes are advantageous since cyclodextrins obtained by the processes have no toxicity of the solvents so that they can widely be used in the field of medicines or foods. However, these processes have some disadvantages: the former process requires complicated operations and the latter process therein OH type of anion exchange resin is used is not sufficient to effectively and continuously produce cyclodextrins because elution rate of reducing sugars adsorbed on the resin is too low and, if HCl is used to increase the elution rate, a regeneration of the resin after HCl elution is required and further, a temperature of liquid passing through the column packed with the resin should be controlled below 20.degree. C. in order to prevent reducing sugars adsorbed from decomposing. In addition, the aforementioned non-solvent processes are those for producing .beta.-cyclodextrin or a mixture of .alpha.-, .beta.- and .gamma.-cyclodextrins but are not those for selectively separating .alpha.-cyclodextrin or .gamma.-cyclodextrin.
As it is well known, cyclodextrins (in particular, .alpha.-cyclodextrin) which have special molecular structure and properties and from which possible utilization in a wide field is expected, may extremely be useful in view of an industrial and an economic points, if such cyclodextrins could be produced advantageously without using any organic solvents.